Imidazole → HCID 24967592, compound

HRID 1409604Notes

Reaction equation

HRID 1409604 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([OH:6])=O.N1[CH:16]=[CH:15]N=C1.C(Cl)(=O)C.Cl.[NH2:22][CH:23]1[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]1=[O:30].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[Cl:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:2]2[C:3]=1[C:4](=[O:6])[N:22]([CH:23]1[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]1=[O:30])[C:15]([CH3:16])=[N:1]2

Participants

8

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 750712-Amino-6-chlorobenzoic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Product 1

HCID 24967592HCID 24967592, compoundYield 32.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-6-chlorobenzoic acid (2.3 g, 13 mmol) and imidazole (1.1 g, 16 mmol) in acetonitrile (25 mL), was added acetyl chloride (1.1 mL, 16 mmol) at room temperature. The mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (2.2 g, 13 mmol), imidazole (2.0 g, 30 mmol) and triphenyl phosphite (4.2 mL, 16 mmol) and heated to reflux for 22 hours. To the mixture, was added water (60 mL). The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL) to give a white solid, which was purified with preparative HPLC (C18 20/80 CH3CN/H2O) to give 3-(5-chloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (1.3 g, 31% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 25/75 CH3CN/0.1% H3PO4, 4.16 min (99.9%); mp: 315° C. (decomp); 1H NMR (DMSO-d6) δ 2.13-2.19 (m, 1H, CHH), 2.57-2.68 (m, 5H, CH3, 2CHH), 2.78-2.85 (m, 1H, CHH), 5.23 (dd, J=5, 11 Hz, 1H, NCH), 7.51-7.58 (m, 2H, Ar), 7.74 (t, J=8 Hz, 1H, Ar), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.63, 23.48, 30.53, 56.61, 117.14, 126.18, 128.98, 132.24, 134.52, 149.27, 155.99, 158.39, 169.38, 172.56; LCMS: MH=306, 308; Anal Calcd for C14H12N3O3Cl+1H2O: C, 51.94; H, 4.36; N, 12.98; Cl, 10.95. Found: C, 51.91; H, 4.24; N, 12.93; Cl, 10.20.

Workup

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL)
  5. customto give a white solid, which
  6. customwas purified with preparative HPLC (C18 20/80 CH3CN/H2O)

Sources & evidence

ORD record
ord-a26bb99df23c4229b6376a759344ab14
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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